Establishment of histopathological diagnostic criteria based on the visualization of HIF-1alpha-expressing quiescent stem-like tumor cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592164
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Yamaguchi University
• Principal Investigator: IKEDA Eiji 山口大学, 医学(系)研究科(研究院), 教授 (30232177)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Michiyasu 山口大学, 大学院医学系研究科, 教授 (80196873)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: グリオーマ / 腫瘍幹細胞 / 低酸素 / ニッチ

Outline of Final Research Achievements

Despite advances in therapy, the clinical course of glioma still remains unfavorable. In this study, we aimed to determine the therapeutic targets for improving the prognosis of glioma. A small subpopulation of HIF-1α-expressing quiescent stem-like tumor cells were successfully specified and visualized exclusively in glioblastoma, the highest grade of glioma, as the candidate for real culprit of its unfavorable prognosis. These cells were concentrated in the zone between a large ischemic necrosis and blood vessels, suggesting that moderately hypoxic microenvironment is their niche. By modelling their niche with spheroids of cultured glioblastoma cells, the emergence of HIF-1α-expressing quiescent stem-like tumor cells was shown to enhance the tumorigenicity. Therefore, a small subpopulation of tumor cells and their niche which were visualized in this study must be the foci of new histopathological diagnostic criteria reflecting real therapeutic targets to eradicate glioma cells.

Free Research Field

病理学